Åke Borg
Principal investigator
Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations
Author
Summary, in English
Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.
Department/s
- Division of Clinical Genetics
- Computational Biology and Biological Physics - Has been reorganised
- Breastcancer-genetics
- Mathematics (Faculty of Engineering)
- Paediatrics (Lund)
- The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
Publishing year
2005
Language
English
Pages
1042-1050
Publication/Series
Leukemia
Volume
19
Issue
6
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Cancer and Oncology
Keywords
- cDNA microarray
- AML
- CML-BC
- ALL
- pediatric leukemia
Status
Published
Research group
- The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
ISBN/ISSN/Other
- ISSN: 1476-5551